3D-Wound healing model: Influence of morphine and solid lipid nanoparticles

Abstract

For efficient pain reduction in severe skin wounds, topically applied opioids may be a new option. Moreover, by stimulating keratinocyte migration opioids may also accelerate wound healing. Yet, conventional formulations failed to consistently provide sufficient pain control in patients which may be due to local drug degradation or insufficient concentrations at the target site. After having excluded major morphine glucuronidation by keratinocytes and fibroblasts, we next aimed for an optimised formulation. Since long intervals for painful wound dressing changes are intended, the formulations should allow for prolonged opioid release and should not impair the healing process. We developed morphine-loaded solid lipid nanoparticles (SLN, mean size about 180nm), and tested improvement of wound closure in a new human-based 3D-wound healing model. Standardised wounds were induced by CO2-laser irradiation of reconstructed human full-thickness skin equivalents (EpiDermFT™). Morphine, morphine-loaded and unloaded SLN accelerated reepithelialization. Keratinocytes almost completely covered the dermis equivalent after 4 days, which was not the case when applying the vehicle. In conclusion, acceleration of wound closure, low cytotoxicity and irritation as well as possible prolonged morphine release make SLN an interesting approach for innovative wound management.